Fatigue could be an important baseline stratification factor for cancer treatment, according to data presented during the 2020 ASCO Quality Care Symposium.1
An analysis of four SWOG treatment trials has found an association between patient fatigue and outcomes in advanced cancer. Data from the retrospective study showed that oncology trial participants with clinically significant fatigue at baseline experienced more adverse events and had worse overall survival than participants without clinically significant fatigue.
These results confirm previous work linking patient-reported outcomes to cancer outcomes and suggest fatigue may be a surrogate marker for performance status, according to the study authors.
“Fatigue is an important baseline stratification factor that should be considered in all oncology treatment trials,” said lead study author, Julia Mo, BS, a medical student at the University of Rochester School of Medicine and Dentistry, Rochester, New York. “Furthermore, clinically significant fatigue should be measured and ameliorated wherever possible among patients with advanced cancer.”
As Ms. Mo explained, fatigue is the most frequently reported symptom in patients with cancer. Although prior studies have suggested that patient-reported outcomes may be associated with cancer outcomes, fatigue is rarely studied separately as a predictor of outcomes.
Study Methodology
For this study, Ms. Mo and colleagues evaluated the association between clinically significant fatigue and the incidence of adverse events, change in quality of life from baseline, and overall survival during cancer treatment. The researchers selected four phase II or III randomized SWOG treatment trials: two trials in advanced non–small cell lung cancer and two trials in advanced hormone-refractory prostate cancer.
“Our results showed a consistent and statistically significant decrease in overall survival associated with baseline clinically significant fatigue.”— Julia Mo, BS
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According to Ms. Mo, the trials used comparable fatigue instruments: the Functional Assessment of Cancer Therapy: General (FACT-G), which has one question on fatigue (“I have a lack of energy”), or the EORTC QLQ-C30, which has three questions on fatigue that combine to form a symptom score. All four chemotherapy trials also had at least 100 quality-of-life respondents at baseline.
Fatigue scores were not evaluated as a continuous variable, said Ms. Mo. Rather, clinically significant fatigue at baseline was defined as a rating of at least 2 on the FACT fatigue survey question or an EORTC QLQ-C30 fatigue symptom score of at least 50%. Only grade 3 to 5 adverse events were considered for incidence analysis.
Finally, researchers employed numerous statistical tests to determine significance, including linear regression models, equality of proportions chi-squared tests, Kaplan-Meier survival estimates, and Cox regression models. Of note, said Ms. Mo, for quality-of-life subscales and overall survival probabilities, researchers controlled for clinical factors such as age and sex and, if available, lab data for serum albumin and hemoglobin levels. Ms. Mo and colleagues also controlled for study-specific stratification factors.
Higher Risk of Mortality With Baseline Fatigue
As Ms. Mo reported, approximately 52% of the 1,907 patients included in the analysis had clinically significant fatigue at baseline. For the studies that collected laboratory data, the average baseline serum albumin and hemoglobin levels were within normal range.
KEY POINTS
- Analysis of four SWOG treatment trials has found that participants with clinically significant fatigue at baseline experienced more adverse events and had worse survival than participants without clinically significant fatigue.
- Patient-reported outcomes and symptoms play a key role in treating these patients.
Analysis of the prostate cancer studies showed that participants who reported baseline clinically significant fatigue were more likely to experience neurologic symptoms and constitutional symptoms, including treatment-related fatigue. Analysis of the lung cancer studies, however, detected no statistical differences in the incidence of adverse events according to baseline fatigue.
Patients with baseline clinically significant fatigue were also found to experience significantly lower quality-of-life domains at baseline compared with those without clinically significant fatigue. However, emotional well-being was the only metric to change significantly from baseline in fatigued vs nonfatigued patients, and it was observed only in prostate cancer studies, said Ms. Mo.
Finally, across all four studies, baseline clinically significant fatigue was associated with a 30% to 50% increased risk of mortality.
“Our results showed a consistent and statistically significant decrease in overall survival associated with baseline clinically significant fatigue,” said Ms. Mo. “Moving forward, we want to explore whether fatigue could be a good marker for stopping treatment or even changing the course of treatment.”
DISCLOSURE: Ms. Mo reported no conflicts of interest.
REFERENCE
1. Mo J, Darke A, Guthrie KA, et al: The association of patient fatigue and outcomes in advanced cancer: An analysis of four SWOG treatment trials. 2020 ASCO Quality Care Symposium. Abstract 140.
